IgE and non-IgE food allergy: A review of immunological mechanisms.

Background: Food allergic (FA) conditions have been classified as immunoglobulin E (IgE) and non-IgE-mediated reactions that affect as many as 8% of young children and 2% of adults in Western countries, and their prevalence seems to be rising. Although the immunologic basis of IgE-mediated FA is well established, the mechanisms that govern non-IgE-mediated FA are not well understood and are marked by a paucity of comprehensive insights. Objective: The purpose of the present report is to examine the current classification and epidemiology of non-IgE-mediated FA, the latest immunologic mechanisms that underlie the three most commonly cited non-IgE FA conditions, viz., eosinophilic esophagitis, food protein-induced enterocolitis, and food protein-induced allergic proctocolitis, and explore what allergist/immunologists in practice should be aware of with regard to the condition. Methods: An extensive research was conducted in medical literature data bases by applying terms such as FA, non-IgE allergy, tolerance, unresponsiveness, cytokines, CD4+ T helper cell pathways, and key cytokine pathways involved in FA. Results: Current evidence now supports the view that immune dysregulation and cytokine-induced inflammation are the fundamental bases for both IgE- and non-IgE-mediated FA. The existing non-IgE-related FA literature is mostly characterized by a relative dearth of mechanistic information in contrast to IgE-mediated FA, in which the immunologic underpinnings as a T helper type 2 directed entity are well established. Although the need for future methodologic research and adherence to rigorous scientific protocols is essential, it is also necessary to acknowledge past contributions that have given much to our understanding of the condition. In the present report, a novel signature cytokine-based classification of IgE-mediated and non-IgE-mediated allergy is proposed that may offer a novel template for future research in the field of non-IgE-mediated FA. Conclusion: The present report provides an overview of the current classification and frequency of IgE- and non-IgE-mediated FAs, and offers insights and potential solutions to address lingering questions, particularly when concerning the latest immunologic mechanisms that underlie the pathogenesis of non-IgE-mediated FA. Although some progress has been made in recent years toward making diagnostic and treatment options available for these conditions, there still remain many lingering questions and concerns to be addressed, which can be fully understood by future research.

The Glasgow Coma Scale and Full Outline of Unresponsiveness score evaluation to predict patient outcomes with neurological illnesses in intensive care units in West Bank: a prospective cross-sectional study.

BACKGROUND: Determining the clinical neurological state of the patient is essential for making decisions and forecasting results. The Glasgow Coma Scale and the Full Outline of Unresponsiveness (FOUR) Scale are commonly used tools for measuring behavioral consciousness. This study aims to compare scales among patients with neurological disorders in intensive care units (ICUs) in the West Bank. METHODS: A prospective cross-sectional design was employed. All patients admitted to ICUs who met inclusion criteria were involved in this study. Data were collected from from An-Najah National University, Al-Watani, and Rafedia Hospital. Both tools were used to collect data. RESULTS: A total of 84 patients were assessed, 69.0% of the patients were male, and the average length of stay was 6.4 days. The mean score on the Glasgow Coma scale was 11.2 on admission 11.6 after 48 hours, and 12.2 on discharge. The mean FOUR Scale score was 12.2 on admission, 12.4 after 48 hours, and 12.5 at discharge. CONCLUSIONS: This study indicates that both the Glasgow Coma Scale and the FOUR scale are effective in predicting outcomes for neurologically deteriorated critically ill patients. However, the FOUR scale proved to be more reliable when assessing outcomes in ICU patients.

Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study.

BACKGROUND: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). METHODS: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). RESULTS: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). CONCLUSION: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.

Full Outline of Unresponsiveness Score versus Glasgow Coma Scale in Predicting Clinical Outcomes in Altered Mental Status.

Introduction: Full outline of unresponsiveness (FOUR) score has advantages over Glasgow Coma Scale (GCS); as it can be used in intubated patients and provides greater neurological details. It has been studied mainly in the trauma and neuroscience setting. Our primary objective was to compare the FOUR versus GCS score as predictors of mortality at 30 days and poor functional outcome at 3 months among nontrauma patients in the emergency department (ED). Methods: This prospective observational study was conducted on adult patients presenting with altered mental status (duration <7 days) in the ED (March 2019-November 2020). Data collection included demographic and clinical features, the GCS and FOUR scores, the feasibility of acquiring and interpreting FOUR on a Likert scale, duration of hospital stay, 30-day mortality, and functional outcome at 3 months on the modified Rankin Scale. Trained emergency medicine residents managing the patient collected the data. The area under receiver's operating characteristics curve (AUROC) was used to compare the accuracy of the GCS and FOUR scores in predicting outcomes. The FOUR score equivalent of GCS cutoffs for categorizing neurological impairment (mild, moderate, and severe) was also investigated. Results: Two hundred and ninety-one patients were included, with a mean age of 50.3 years and 67.4% males. Most patients (40.2%) had altered mental status for 1-3 days and hepatic encephalopathy was the most common ED diagnosis. The mortality at 30 days was 66.7% (194 of 291), and 88% (256 of 291) of patients had poor functional outcomes at 3 months. The AUROCs for predicting 30-day mortality were similar for both the scores (GCS: 0.70, FOUR: 0.71, and the P value for difference: 0.9). Similarly, the AUROCs for predicting 3-month poor functional outcome were 0.683 and 0.669 using GCS and FOUR, respectively, with a nonsignificant difference (P = 0.82). The FOUR score strata of 14-16, 11-13, and 0-10 were found to be equivalent to the GCS scores of 13-15 (mild), 9-12 (moderate), and 3-8 (severe). The feasibility of acquiring and interpreting GCS and FOUR scores on the Likert scale was found to be "easy." Conclusion: The FOUR score is similar to GCS in predicting mortality at 30 days and poor neurological outcomes at 3 months among nontrauma patients of ED. Moreover, it was found that the FOUR score is "easy" to assess and interpret by the emergency residents.

EEG signature of near-death-like experiences during syncope-induced periods of unresponsiveness.

During fainting, disconnected consciousness may emerge in the form of dream-like experiences. Characterized by extra-ordinary and mystical features, these subjective experiences have been associated to near-death-like experiences (NDEs-like). We here aim to assess brain activity during syncope-induced disconnected consciousness by means of high-density EEG monitoring. Transient loss of consciousness and unresponsiveness were induced in 27 healthy volunteers through hyperventilation, orthostasis, and Valsalva maneuvers. Upon awakening, subjects were asked to report memories, if any. The Greyson NDE scale was used to evaluate the potential phenomenological content experienced during the syncope-induced periods of unresponsiveness. EEG source reconstruction assessed cortical activations during fainting, which were regressed out with subjective reports collected upon recovery of normal consciousness. We also conducted functional connectivity, graph-theoretic and complexity analyses. High quality high-density EEG data were obtained in 22 volunteers during syncope and unresponsiveness (lasting 22±8 s). NDE-like features (Greyson NDE scale total score ≥7/32) were apparent for eight volunteers and characterized by higher activity in delta, theta and beta2 bands in temporal and frontal regions. The richness of the NDE-like content was associated with delta, theta and beta2 bands cortical current densities, in temporal, parietal and frontal lobes, including insula, right temporoparietal junction, and cingulate cortex. Our analyses also revealed a higher complexity and that networks related to delta, theta, and beta2 bands were characterized by a higher overall connectivity paralleled by a higher segregation (i.e., local efficiency) and a higher integration (i.e., global efficiency) for the NDE-like group compared to the non-NDE-like group. Fainting-induced NDE-like episodes seem to be sustained by surges of neural activity representing promising markers of disconnected consciousness.

Long-Term Adherence and Risk of Allergic Reactions in Patients Who Attained Milk Oral Immunotherapy Maintenance.

BACKGROUND: Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse. OBJECTIVE: We aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions. METHODS: Patients who completed milk OIT and reached a maintenance dose of 200 mL of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and the adherence to OIT maintenance protocol. RESULTS: The cohort consisted of 50 patients. Only 56% of the cohort adhered to the protocol, which consisted of ingesting a minimum of 200 mL of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions as well as a reduced incidence of anaphylaxis, health care/emergency room visits, and epinephrine/antihistamine administration. CONCLUSIONS: The findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms.

Unresponsiveness to Chiari Malformation Type I Surgery Can Be Related to the Accompanying Chiari Network.

Surgical treatment is indicated for Chiari malformation type 1 (CMI) with tonsillar descent (TD) of >5 mm and other clinical manifestations. However, some patients remain unresponsive to surgery; this is an active topic of discussion. A patient presented to the emergency department with dizziness and an impaired gait. He had a history of hypertension. Magnetic resonance investigations revealed a 9-mm TD and cervical syringomyelia. There was no evidence of interatrial septum pathology on transthoracic echocardiography performed preoperatively. Although his complaints were attributed to CMI and surgery was performed, his symptoms remained persistent. Two years later, when the patient's dizziness increased, a posterior fossa transient ischemic attack (TIA) was suspected. A large patent foramen ovale (PFO) and Chiari network (CN) were also detected on transesophageal echocardiography. His complaints were resolved following PFO closure. Our case suggests that neurosurgeons should be informed about the results of the companionship of a PFO and CN. Before deciding on CMI surgery for patients with only dizziness complaints, a detailed investigation of accompanying cardiac pathologies is paramount to ensure accurate diagnosis and treatment.

Comparison of Glasgow Coma Scale and Full Outline of UnResponsiveness score to assess the level of consciousness in patients admitted to intensive care units and emergency departments: A quantitative systematic review.

OBJECTIVES: We aimed to investigate the reliability and validity of the Glasgow Coma Scale (GCS) and the Full Outline of UnResponsiveness (FOUR) score used by nurses and physicians to assess the level of consciousness in patients admitted to intensive care units (ICUs) and emergency departments (EDs). REVIEW METHOD USED: This systematic review was guided by the Cochrane Handbook for Systematic Reviews of Interventions and followed the reporting standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis Statement. DATA SOURCES: A systematic search was conducted using the following databases: CINAHL, MEDLINE, and EMBASE. REVIEW METHODS: All authors performed the study selection process, data collection, and assessment of quality. The following psychometric properties were addressed: inter-rater reliability, internal consistency, and construct validity. RESULTS: Six articles were included. The GCS and the FOUR scores demonstrated excellent reliability and very strong validity when used by nurses and physicians to assess the level of consciousness in patients admitted to the ICU and ED. The FOUR score demonstrated slightly higher overall reliability and validity than the GCS. CONCLUSION: This systematic review indicates that the FOUR score is especially suitable for assessing the level of consciousness in patients admitted to the ICU and ED. The FOUR score demonstrated higher reliability and validity than the GCS, making it a promising alternative assessment scale, despite the GCS's longstanding use in clinical practice.

Comparison of the Prognostic Accuracy of Full Outline of Unresponsiveness (FOUR) Score with Glasgow Coma Scale (GCS) Score among Patients with Traumatic Brain Injury in a Tertiary Care Center.

Objectives The Glasgow Coma Scale (GCS) is widely used and considered the gold standard in assessing the consciousness of patients with traumatic brain injury. However, some significant limitations, like the considerable variations in interobserver reliability and predictive validity, were the reason for developing the Full Outline of Unresponsiveness (FOUR) score. The current study aims to compare the prognostic accuracy of the FOUR score with the GCS score for in-hospital mortality and morbidity among patients with traumatic brain injury. Materials and Methods A prospective cohort study was conducted, where 237 participants were selected by consecutive sampling from a tertiary care center. These patients were assessed with the help of GCS and FOUR scores within 6 hours of admission, and other clinical parameters were also noted. The level of consciousness was checked every day with the help of GCS and FOUR scores until their last hospitalization day. Glasgow Outcome Scale was used to assess their outcome on the last day of hospitalization. The GCS and FOUR scores were compared, and data were analyzed by descriptive and inferential statistics. The chi-square test, independent Student's t -test, and receiver operating characteristic analysis were used for inferential analysis. Results The area under the curve (AUC) for the GCS score at the 6th hour for predicting mortality was 0.865 with a cutoff value of 5.5, and it yields a sensitivity of 87% and a specificity of 64%. The AUC for FOUR scores at the 6th hour for predicting the mortality was 0.893, with a cutoff value of 5.5, and it yields a sensitivity of 87% and a specificity of 73%. Conclusion The current study shows that, as per the AUC of GCS and FOUR scores, their sensitivity was equal, but specificity was higher in the FOUR score. So, the FOUR score has higher accuracy than the GCS score in the prediction of mortality among traumatic brain injury patients.

Oral Immunotherapy: An Overview.

Oral immunotherapy (OIT) is an alternative treatment of IgE-mediated food allergy that has been shown to increase tolerance threshold to many of the top food allergens, although this effect may be dependent on age, dose, frequency, and duration. OIT has been shown to be effective and safe in infants, and early initiation can improve rates of desensitization even for those foods whose natural history favors loss of allergy. Studies looking at protocol modification to improve OIT success are ongoing as is the evaluation of clinical tools to help monitor OIT effects.

Assessment of GCS and FOUR Score as Prognostic Indicators for Hospital Stay and Morbidity in Traumatic Brain Injury Patients: An Observational Study.

Aim: The objective of the present research was to evaluate variations in hospital stay as well as morbidity based on the Glasgow Coma Scale (GCS) and Full Outline of Un-Responsive (FOUR) scores for patients who had traumatic brain injury (TBI). Materials and Methods: A total of 107 patients with TBI patients who attended the emergency department of MES Medical College, Perinthalmanna, were enrolled into the study. FOUR and GCS scoring systems were used to assess the patients within 24 hours of the presentation to the emergency department. Both FOUR and GCS scoring systems were assessed at the same time. The outcome was measured in terms of length of hospital stay and morbidity, which was assessed using modified Rankin score. Chi-square test was used to calculate sensitivity, specificity, positive predictive value, and negative predictive value. The area under the curve (AUC) was calculated using receiver operating characteristic curve analysis. A P value <0.05 was considered significant. Results: We found a strong positive correlation between GCS and FOUR score with a Spearman coefficient of 0.9. Comparison of AUC between GCS score and FOUR score showed a statistically significant difference (P = 0.0044), predicting that FOUR score was a better predictor of hospital stay (>15 days) than GCS score. Comparison of AUC between GCS score and FOUR score showed a significant statistical difference (P = 0.0002), showing that FOUR score was a better predictor of morbidity than GCS. Conclusion: FOUR score was a better predictor of hospital stay and morbidity as compared to GCS score.

Modulation of Corticospinal Excitability during Action Observation in Patients with Disorders of Consciousness.

Brain imaging studies have recently provided some evidence in favor of covert cognitive processes that are ongoing in patients with disorders of consciousness (DoC) (e.g., a minimally conscious state and vegetative state/unresponsive wakefulness syndrome) when engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer's motor system maps others' actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, considering that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. The results indicate that some form of motor resonance is spared in a subset of patients with DoC, with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether diagnosed with VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and the difference between the resonance with biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials, following the stimulation of the median nerve at the wrist (i.e., the temporal marker signaling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.

Comparison of Glasgow Coma Scale Full Outline of UnResponsiveness and Glasgow Coma Scale: Pupils Score for Predicting Outcome in Patients with Traumatic Brain Injury.

Background: Glasgow coma scale (GCS) score is the most widely used clinical score for the initial assessment of neurologically injured patients and is also frequently used for prognostication. Other scores such as the Full Outline of UnResponsivness (FOUR) score and the Glasgow Coma Scale-Pupils (GCS-P) score have been more recently developed and are gaining popularity. This prospective cohort study was conducted to compare various scores in terms of their ability to predict outcomes at 3 months in patients with traumatic brain injury (TBI). Materials and methods: The study was carried out between October 2020 and March 2022. Patients who presented to the hospital with TBI were assessed for inclusion. Initial coma scores were assessed in the emergency department and again after 48 hours of admission. Outcome was assessed using the extended Glasgow outcome score (GOSE) at 3 months after injury. The receiver operating curve (ROC) was plotted to correlate coma scores with the outcome, and the area under the curve (AUC) was compared. Results: A total of 355 patients with TBI were assessed for eligibility, of which 204 patients were included in the study. The AUC values to predict poor outcomes for initial GCS, FOUR, and GCS-P scores were 0.75 each. The AUC values for 48-hour coma scores were 0.88, 0.87, and 0.88, respectively. Conclusion: The GCS, FOUR, and GCS-P scores were found to be comparable in predicting the functional outcome at 3 months as assessed by GOSE. However, coma scores assessed at 48 hours were better predictors of poor outcomes at 3 months than coma scores recorded initially at the time of hospital admission. How to cite this article: Chawnchhim AL, Mahajan C, Kapoor I, Sinha TP, Prabhakar H, Chaturvedi A. Comparison of Glasgow Coma Scale Full Outline of UnResponsiveness and Glasgow Coma Scale: Pupils Score for Predicting Outcome in Patients with Traumatic Brain Injury. Indian J Crit Care Med 2024;28(3):256-264.

Unveiling the Complexity of Traumatic Brain Injury: Insights from Clinical Scoring Systems.

Krishnakumar M. Unveiling the Complexity of Traumatic Brain Injury: Insights from Clinical Scoring Systems. Indian J Crit Care Med 2024;28(3):193-195.

Ethical issues of nosology in disorders of consciousness.

The current classification scheme for severe disorders of consciousness (DoC) has several shortcomings. First, there is no consensus on how to incorporate patients with covert consciousness. Second, there is a mismatch between the definitions of severe DoC, based on consciousness, and the diagnosis of these same DoC, which is based on observable motoric responsiveness. Third, current categories are grouped into large heterogeneous syndromes which share phenotype, but do not incorporate underlying pathophysiology. Here we discuss several ethical issues pertaining to the current nosology of severe DoC. We conclude by proposing a revised nosology which addresses these shortcomings.

Evaluation of bone marrow findings in hemodialysis patients with erythropoietin-resistant anemia.

INTRODUCTION: Treatment with erythropoietin-stimulating agents (ESAs) is widely used in anemia of chronic kidney disease (CKD). Acquired ESA resistance is an important problem. The aim of this study is to examine the bone marrow findings in hemodialysis patients with ESA-resistant anemia. METHODS: The data of 210 patients with acquired ESA resistance were reviewed retrospectively. The patients were divided into groups according to having diagnosis of dysplasia and hematological disease, and survival analysis was performed. RESULTS: A total of 26 patients were included in the study. While dysplasia was present in 10 (38.5%) patients, five of them were diagnosed hematologically. When survival analysis was performed between those with and without a hematological diagnosis, a difference in survival was observed against the group with the diagnosis (24.4 vs. 72 months, p = 0.045). CONCLUSION: Unresponsiveness to ESA treatment in CKD patients or a decrease in one of the other cell lines along with hemoglobin, it would be appropriate to perform early bone marrow examination.

In vitro antileishmanial activity of thioridazine on amphotericin B unresponsive/ sensitive Leishmania donovani promastigotes and intracellular amastigotes.

The recent increase in the drug (liposomal amphotericin-B) unresponsive cases becomes hostile for the visceral leishmaniasis (VL) elimination target. The quest for new antileishmanial drugs is on the way and may demand more time. Meanwhile, drug repurposing is a quite promising option to explore further. We made such an attempt with thioridazine (TRZ), a first-line antipsychotic drug, which was reported for antimicrobial activity. In this study, we evaluated the drug activity of TRZ against amphotericin-B (Amp-B) sensitive and unresponsive Leishmania donovani promastigotes, as well as intracellular amastigotes (drug sensitive). We observed a potent antileishmanial activity of TRZ with significantly low half maximal inhibitory concentrations (IC50) on both the variants of promastigotes (0.61 ± 0.15 µM). These concentrations are comparable to the previously reported IC50 concentration of the current antileishmanial drug (Amp-B) against L. donovani. Light microscopy reveals the perturbations in promastigote morphology upon TRZ treatment. The in vitro studies on human macrophage cell lines determine the 50% cytotoxicity concentration (CC50) of TRZ on host cells as 20.046 µM and a half maximal effective concentration (EC50) as 0.91 µM during L. donovani infection, in turn selectivity index (SI) was calculated as 22.03 µM. Altogether, the results demonstrate that TRZ has the potential for drug repurposing and further studies on animal models could provide better insights for VL treatment.

Interaction Between Baseline Participant Factors and Treatment Effects Following Peanut Oral Immunotherapy.

BACKGROUND: The Probiotic Peanut Oral Immunotherapy-003 multicenter randomized trial found that both probiotic peanut oral immunotherapy (PPOIT) and peanut OIT alone (OIT) were effective compared with placebo in inducing clinical remission after 18 months of treatment, and improving health-related quality of life (HRQL) at 12 months after treatment. Understanding treatment effect modifiers can optimize outcomes through precision care. OBJECTIVES: This post hoc study examined baseline clinical and demographic participant factors that modified treatment effects. METHODS: The study sample included 201 children (aged 1-10 years) with challenge-confirmed peanut allergy. Exposure variables were baseline clinical and demographic factors. Outcomes were remission (double-blind, placebo-controlled food challenge, cumulative 4,950-mg peanut protein at 8 weeks after treatment) and HRQL (change in Food Allergy Quality of Life Questionnaire-Parent Form score). Interactions between baseline factors and treatment effects on remission and HRQL were explored with regression models. RESULTS: A higher degree of peanut sensitivity (large peanut skin prick test, high peanut specific IgE, and low reaction-eliciting dose at study entry challenge) and other concurrent allergic conditions (multiple food allergies, asthma, or wheeze) were associated with the decreased likelihood of attaining remission after both PPOIT and OIT treatment. History of anaphylaxis was associated with the reduced likelihood of remission after PPOIT compared with OIT. For the HRQL outcome, there was evidence that sex, history of anaphylaxis, and age modified treatment effects. CONCLUSIONS: Baseline participant factors modify PPOIT and OIT effects on remission and HRQL. Considering modifiers of treatment effect during participant selection may optimize treatment success and clinical trial design toward specific outcomes, such as the achievement of remission.

Similarities in consciousness occurring during sleep and sedation.

The subjective experiences of sedation or anaesthesia are underexplored. A recent study by Valli and colleagues (Br J Anaesth 2023; 131: 348-59) found similar frequency and content of recalled experiences after both non-rapid eye movement sleep and target-controlled infusions of propofol or dexmedetomidine titrated to verbal unresponsiveness. The authors find that the phenomenological similarities between consciousness during sleep and sedation mirror their physiological similarities. Intriguingly, in this small sample, conscious experience did not show a dose-dependent response suggesting other factors are important in determining the propensity for consciousness under sedation.